EVALUATION OF A SYSTEM FOR REAL-TIME MEASUREMENT OF ANESTHETIC UPTAKE

EVALUATION OF A SYSTEM FOR REAL-TIME MEASUREMENT OF ANESTHETIC UPTAKE

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University Miaxxilms International

300 N. Zeeb Road Ann Arbor, Ml 48106

1328679

Navabi, Mohammad Jafar

EVALUATION OF A SYSTEM FOR REAL-TIME MEASUREMENT OF ANESTHETIC UPTAKE

The University of Arizona M.S. 1986

University Microfilms

International

EVALUATION OF A SYSTEM FOR REAL-TIME MEASUREMENT OF ANESTHETIC UPTAKE

by

Mohammad Jafar Navabf

A Thesis Submitted to The Faculty of the DEPARTMENT OF ELECTRICAL AND COMPUTER ENGINEERING

In Partial Fulfillment of the Requirements For the Degree of

MASTER OF SCIENCE

WITH A MAJOR IN ELECTRICAL ENGINEERING In the Graduate Col lege

THE UNIVERSITY OF ARIZONA

1 9 8 6

STATEMENT BY AUTHOR

This thesis has been submitted in partial fulfillment of requirements for an advanced degree at The University of Arizona and is deposited in the University Libraray to be made available to borrowers under rules of the Library.

Brief quotations from this thesis are allowable without special permission, provided that accurate acknowledgment of source is made. Requests for permission for extended quotat1 on from or reproduct i on of th1s manuscript in whole or in part may be granted by the head of the major department or the Dean of the Graduate College when in his or her Judgment the proposed use of the material is in the interests of scholarship. In all other Instances, however, permission must be obtained from the author.

SIGNED

APPROVAL BY THESIS DIRECTOR

This thesis has been approved on the date shown below:

K. C. Mt^REf / Date

Associate Professor of Electrical Engineering

ACKNOWLEDGMENTS

I would 1 ike to thank Dr. Kenneth C. Mylrea and Dr. Reynolds J. Saunders for their support and continued guidance throughout this project. I will always remember and appreciate their patience and understanding.

i 11

TABLE OF CONTENTS

Page

LIST OF ILLUSTRATIONS . ^{. . V}

LIST OF TABLES . . vi

ABSTRACT vi i

1. INTRODUCTION AND BACKGROUND 1

2. MATHEMATICAL MODEL 7

3. ERROR ANALYSIS 14

4. IMPLEMENTATION 19

Hardware Description 19

Software Description 21

5. SYSTEM EVALUATION 25

Computer's Software/Hardware Tests 25

Overall System Evaluation 26

6. RESULTS 35

7. DISCUSSION OF RESULTS 54

LITERATURE REFERENCES 58

i v

LIST OF ILLUSTRATIONS

F i gure Page

2.1. Typical changes In concentration with time

during induction of anesthesia . . 8 2.2. Typica] changes In concentration with time

during emergence from anesthesia 8 2.3. Block diagram of anesthetic monitoring system . . 10 2.4. Typical concentration and flow maveforms illus-

strating time delay in concentration signal ... 13 3.1. Assumed waveform for flow signals in the

analysis of errors 16

3.2. Assumed concentration waveform for the analysis

of errors 17

4.1. Flow-meter calibration data 22

5.1. Test sytem used for induction and emergence

simulation 28

5.2. Test system used for zero-uptake simulation . . . 30 5.3. Uptake of anesthetic by spirometer water .... 31 6.1. Breath by breath uptake measured during induc­

tion trial #2 49

6.2. Cumulative uptake results for Induction and

emergence tests 50

v

LIST OF TABLES

Table Page

6.1. Breath to breath results for emergence

trial #8 36

6.2. Results of emergence tests 38

6.3. Breath to breath results for Induction

trial #2 41

6.4. Results of induction tests 43

6.5. Breath to breath results for zero-uptake

trial #4 45

6.6. Results of zero-uptake tests 47 6.7. Results of induction tests with on-line

breath-by-breath bias adjustment 52

v i

ABSTRACT

The initial work Involved the analysis of sources of errors in an anesthetic uptake measurement system.

After completing the error analysis appropriate measurement instruments were selected and a computer program for real-time breath to breath analysis of anesthetic gases was implemented. The analysis system was evaluated by careful bench tests which slmulted zero uptake, induction, and emergence of anesthesia. The error in the measured volumes ranged from 0.28% to 8.40%.

Cumulative uptake had errors in the range of 0.18% to 8.92%. The system was later revised for on-line breath-by-

breath flow-meter bias adjustment. After the revisions, the error in the measured volumes was less than 3% and cumulative uptake had a worst case difference between the precalculated value and the measureid value of 4.177*.

v 11

CHAPTER 1

INTRODUCTION AND BACKGROUND

In the delivery of general anesthesia the purpose of the anesthesiologist is to raise and maintain the concentration of anesthetic gases in arterial blood high enough to put the patient in a pain free state. At the same time it must be ensured that this concentration does not exceed some limit. Knowledge of anesthetic uptake can provide the anesthesiologist with the necessary information regarding the patient's status and help him/her with decision making. A faster and more precise control of anesthetic administration and a rapid detection of abnormal conditions may also be possible.

After Eger [1] suggested that anesthet i c depth i s correlated with alveolar concentration of anesthetic agent, it was first assumed that knowing the end tidal concentration would help the anesthesiologist in the delivery of anesthesia. This assumption arose from the fact that end-tidal concentration is related to the alveolar concentration of the anesthetic. However it was later determined that end-tidal concentration alone is not a good descriptor of anesthetic uptake because the effects

1

2 of anesthetic may vary greatly as a function of cardiac output or the functional residual capacity.

It is believed that real time anesthetic mass uptake rate and cumulative uptake may correlate closely with anesthetic depth [1]. Anesthetic uptake is currently approximated by the anesthesiologist by relying on available monitoring devices in the operating room. These devices indicate the patient's vital signs such as blood pressure, respiratory rate, heart rate, anesthetic delivery system settings, and also the patient's response to surgical stimulus.

Anesthetic uptake can be approximated by using empirical mathematical models or electrical analogs which describe anesthetic uptake. One such model, developed by Lowe and Ernst [2] is the square root of time model.

Cumulative uptake in a closed circuit anesthetic delivery system was empirically found to follow the relationship:

C.U. = 2 * Ca * Q * <t)^1/2 (eq. 1.1) where C.U. = Cumulative Uptake

Ca = Arterial concentration Q = Cardiac output

t = time elapsed since the start of anesthesia and the constant 2 has units of [ (min) */^]/(conc. 7.).

Empirical models provide a reasonable estimate of anesthetic uptake provided the patient is in the same

3 general health category as the group of people •from which the model was developed. For example the square root of time model depends on many patient parameters such as heart and lung condition and amount of fat in the patient's body. Considering the general increase in average age of our population, the number of patients who do not fit the empirical model is on the rise. Therefore the need for a system that can continuously and accurately measure the uptake of anesthetic agents is clear.

To measure mass uptake and uptake rate a continuous measurement of anesthetic gas concentration and flow is needed. One such system developed by Noe et. al [2], measured expired gas flow volume, carbon dioxide

excretion and oxygen consumption, continuously for two minute periods at 15 minute intervals. COg concentration was measured with an infrared CO^ analyzer, 0£

concentration with a rapid polarographic analyzer, and gas flow rate by a pneumotachograph. A general purpose digital computer was used to process the data. Values of flow volume, carbon dioxide excretion, and oxygen consumption were found for 50 normal women during abdominal surgery.

The results indicated a progressive increase in uptake and a concurrent but not necessarily simultaneous decrease in C02 output. The correlation between rate of decrease in COg excretion and minute volume was studied. It was

4 concluded that with on-line computation a more comprehensive and better controlled study of this relationship would be possible.

In another study conducted by Ramanthan et. al [3], oxygen consumption ana carbon dioxide production

during endotracheal anesthesia was measured in real time.

It was assumed that the total volume of gases leaving the system was approximately equal to the volume of fresh gas entering the system. This volume was measured and multiplied by the oxygen concentration in gases leaving the system, in order to calculate the volume of oxygen leaving the system. Oxygen consumption was calculated as the difference between the oxygen volume entering and leaving the system. Production of CO^ was calculated by multiplying the volume of gases entering the system with the expired C0² concentration.

Chi 1 coat et. al [4] developed a control system to bring the tension of anesthetic agent in the brain to a specified value determined by the anesthetist, and maintain this value until a new value was specified. The inspired concentration required to achieve the desired brain tension was calculated from a model of the patient and set automatically on the vaporizer. During the development of this system inspired and end-tidal concentration of several gases, and alveolar and total

5 ventilation was measured in mechanically ventilated subjects [5]. A quadrupole mass spectrometer was used for measuring gas concentrations and the mixed carbon dioxide concentration was computed as the volume weighted average of expired carbon dioxide. The system was tested on eight Alsatian dogs. After omitting results affected by avoidable errors, the standard deviation of the measured to computed arterial tension ratio was less than 10%.

More recently, Lauria [6] designed and tested a system for real-time analysis of anesthetic gases. The outputs of a gas analyzer and flow-meter were fed into a computer for analysis. The system calculated breath by breath inspired and end-tidal concentration , the ratio of inspired to end-tidal concentration , inspired and expired volume, respiratory rate, single breath uptake of anesthetic, and the square root of time of anesthesia.

Measurements were done in real-time, in laboratory simulation. Due to the computer's speed limitation a 2 seconds interval was necessary between each breath for calculating the variables and outputting the results to the screen. During this interval the signals from the gas analyzer and the flow-meter were not sampled by the computer and not included in the analysis. This produced a potential cause of errors in the measured parameters, and also put a limit of 12 BPM on the maximum breathing rate

6 the system could handle. Cumulative uptake measured by the system during bench tests had a worst case error of 10.67.

while the other measured variables had errors of less than or equal to 5.0 7. .

The objective of this thesis was to determine the feasibility of measuring the uptake of anesthetic agents in real-time using state of the art instrumentation which could be used in the operating room. A further goal of this study was to implement such a system for measurement of anesthetic uptake. These objectives were accomplished by:

1) Analyzing sources of errors in a simulated measurement system and evaluating the contribution of each error to the overall error. Possible sources of errors include gas analyzer and the flow-meter inaccuracies, analog to digital conversion, data reduction, and synchronization between flow and concentration.

2) Implementing a system for anesthetic uptake measurement and evaluating its performance by means of controlled bench tests.

CHAPTER 2 MATHEMATICAL MODEL

During the induction phase of anesthesia in a circle breathing system the patient receives anesthetic gases mixed with oxygen and nitrous oxide from an anesthesia machine. Initially there is no anesthetic in the blood and some of the gases entering the lungs diffuse into the arterial blood. Diffusion occurs rapidly and normally before expiration starts, gases In the alveoli will be In equilibrium with the gas in the blood. Compared to inspired gases, the expired gases will thenhave a lower concentration of anesthetic gas (Figure 2.1).

During emergence from anesthesia, concentration of anesthetic agent in the patient is higher than that of the gas entering the lungs. Thus anesthetic gas will diffuse from the blood to the lungs and cause the expired gas to have a higher concentration of anesthetic agent than the inspired gas (Figure 2.2).

To implement the measurement system we used a commercially available flow-meter and mass spectrometer to continuously measure gas flow Into and out of the patient and the concentration of anesthetic agent In the inspired and expired gases. The outputs from these Instruments are

7

Cone. A

Insp i rat1on

Exp 1 rat1on

T1 me Figure 2.1. Typical changes In concentration with time

during induction of anesthesia

Cone.A Expiration

Insp1 rat1on

Time Figure 2.2. Typical changes In concentration with time

during emergence from anesthesia

9 fed Into a digital computer for analysis and calculations (Figure 2.3).

Inspired and expired volumes are measured as the time integral of the flow signal. Inspired volume Is the integral of the flow wave-form from the beginning of a breath to the end of inspiration:

f INSEND

VINS = F(t) dt (eq* 2*1)

J INSBEG

where Vj^Ng = inspired volume

F(t) = flow signal as a function of time

INSBEG = time corresponding to start of inspiration INSEND = time corresponding to end of inspiration.

The expired volume is the integral of the flow over the

VEXP "J expiration period:

EXPEND

F(t) dt (eq. 2.2)

EXPBEG

where V^^p = expired volume

EXPBEG = time corresponding to start of expiration EXPEND = time corresponding to end of expiration.

Applying the trapezoidal method of integration to equations 2.1 and 2.2 would give rise to:

INSEND

V,^NS = F(i) x T (eq. 2.3)

IND i=INSBEG

1 0

FLOW CONCENTRATION

TRANSDUCER TRANSDUCER

PATIENT ANESTHETIC

MACHINE

MGA-1100 GAS ANALYZER OHMEDA

FLOW-METER

A/D CONVERTER

DISPLAY CALCULATIONS

INTEL SYSTEM 310 MICRO-COMPUTER

F i gure 2.3. Block diagram of anesthetic monitoring system.

1 1 EXPEND

VFXp =2 F (!) X T (eq. 2.4)

tAr 1=EXPBEG

where F(i) = the 1th flow sample

T = time Interval between 2 consecutive samples.

Using the principle of conservation of mass, anesthetic uptake per breath Is equal to the difference between inhaled and exhaled mass. Anesthetic mass fs calculated by multiplying the volume of gas by the volume percent of anesthetic. Uptake per breath is the sum of inspired and expired uptakes where the expired uptake is negati ve.

INSEND EXPEND

U F(i)xC(i)xT F (i) xC (i) xT (eq. 2.5) i = INSBEG i =EXPBEG

where U = Uptake per breath"

C(i) = The 1^th concentration sample.

Since the end of inspiration is the same as the start of expiration (INSEND=EXPBEG) and equation 2.5 can be s i mp11f1ed to:

EXPEND

U F(i) x C(i) x T (eq. 2.6)

1=1NSBEG

In the above equation the flow sample must be multiplied by the corresponding concentration sample.

However the gas analyzer output has an inherent time delay which must be taken into account in the multiplication as per equation 2.7:

1 2

EXPEND

U =2 F(1) x C( 1 ~ 1 d) x T (eq. 2.7) 1=INSBEG

where id = the number of samples corresponding to output delay in gas analyzer.

Figure 2.4 shows typical flow and concentration waveforms and Illustrates the concept of time delay.

The cumulative anesthetic uptake Is the sum of individual breath uptakes over time.

CURRENT

C.U. = U(breath) (eq. 2.8)

b=FIRST

where C.U. = Cumulative Uptake FIRST = first breath

CURRENT = current breath.

Respiratory rate (RR) is calculated as the inverse of time per breath:

RR = 1 / (EXPEND - INSBEG) (eq. 2.9) The last inspired and expired concentrations are used to represent the inspired (CjNS) and end-tidal (C^j) concentrations respectively:

CINS = C(i) at 1 = INSEND <eci- 2.10) CEJ = C(i) at i = EXPEND (eq. 2.11)

13

FLOW

TIM

CONC.

i<—TIME DELAY

TIME

Figure 2.4. Typical concentration and fl trat"

Typ flow waveforms illus­

trating time delay in concentration signal. i t

CHAPTER 3

ERROR ANALYSIS

The purpose of the error analysis was to investigate various sources of error in the measurement system and determine the potential of state of the art instrumentation to provide single breath and cumulative uptake measurements to within ±57.. An analysis of errors was conducted using computer simulation of the measurement system including the errors associated with each component of the system. Errors in the measurement of breath by breath uptake were determined by using typical flow and concentration waveforms as the input to the simulation program. In the computer simulation the following sources of error were considered in the calculation of worst case

error i n breath by breath uptake measurements:

- Concentration accuracy and drift.

- Flow measurement accuracy and drift.

- Timing accuracy of the computer clock.

- Digitizing flow and concentration signals.

- Selecting inspiration and expiration times.

-Digitizing integration techniques.

Estimates were made for the expected errors from the computer and instrumentation in use and the errored

14

15 single breath uptake was calculated. Error free single breath uptake was also calculated by exact integration of the product of flow and concentration waveforms over the period of a breath. Computer calculations were then conducted to determine the overall measurement error. This was calculated as the difference between the errored and the error free signal. Contribution of each of the sources of error in the overall measurement was also calculated.

The estimated value for each of the sources of error was varied and the change in the calculated single breath uptake as a function of this variation was observed.

Figure 3.1 shows the flow waveform used in the error analysis. A sinusoidal shape was assumed for the inspiratory and half of the expiratory signal. A decaying exponential was used for the second half of the expiration signal. Peak flow of 524 ml/sec was produced by taking 500 mL as a typical tidal volume with an inspiration time of 1.5 seconds. The expired waveform had the same peak value, and the time constant for the exponential portion was adjusted so that the inspired and expired volumes were equal. The concentration wave-form of figure 3.2 was assumed with maximum inspiration and expiration concentration levels of 47. and 27. respectively.

\

The results showed that digital integration techniques introduced less than 0.027. error in the

16

FLOWA PEAK FLOW

TIME

F i gure 3.1. Assumed flow waveform for error analysis.

17

CONC

TIM

Figure 3.2. Assumed concentration waveform for error analyst s.

18 measured single breath uptake. The error due to timing of computer system clock will contribute to the overall error directly meaning that 17. error in the timing will produce 17. error in the uptake. However since the computer timing was known to within *0.027.. this error was insignificant.

Determination of the start of inspiration and expiration together with digitizing flow and concentration signals produced 0.137. error. Concentration and flow inaccuracies were directly reflected in the single breath uptake measurement results. Expected errors in the concentration and flow are ±17. and ±57. respectively. Using all of the above assumptions, a total of almost ±77. was observed in the measurement.

Primary contributions to the overal1 error were from the flow and concentration measuring instruments.

Flow-meter bias drift which was not considered in the above analysis, can cause considerable error. A bias variation of +1 LPM resulted in almost 137. mismatch between inspired and expired volumes and from 6.57. to 137.

error in the measured single breath uptake depending on the inspired and expired concentration of anesthetic gas.

Therefore in order to minimize the error in measured uptake, it is necessary to use a flow-meter and a gas analyzer with very low error and bias drift or in some way compensate for the instrument errors.

CHAPTER 4

IMPLEMENTATION

» A system for on-line measurement of anesthetic uptake was implemented. The hardware and software used in this system are described here.

Hardware Description

A Perkin Elmer's medical gas analyzer (MGA 1100) was used to continuously measure concentration of anesthetic agent. The MGA 1100 has an accuracy of ±17. of full scale for nitrogen and oxygen and ±27. for for CO^, nitrous oxide and halothane, a stability of ±27. per month, and a linearity of ±27. of full scale over concentration.

The gas analyzer was calibrated as outlined in the MGA- 1100 Operations And Maintenance Manual.

The gas analyzer draws 60 ml/sec of gas sample through an eight foot sampling tube which creates a fixed delay in the concentration reading. To measure this time delay, a balloon filled with pure oxygen was connected to the transducer of a HP 780-9 pressure monitor causing pressure build-up on the transducer. By breaking the balloon with a needle on the end of the sampling tube, the pressure on the transducer is released instantaneously and at the same time the gas analyzer starts sampling the gas

19

20 which was inside the balloon and after the time delay its output will indicate a change in oxygen concentration from 20% to almost 1007. . The difference between the time when the pressure at the transducer drops and the output of the gas analyzer rises, is the time delay. This value was read on the oscilloscope to be 410 ±5 msec.

For flow measurement a pulsed phase measurement ultrasonic flow-meter developed by Ohmeda Corporation was used. To calibrate the flow-meter it was necessary to compare the flow reading of the Ohmeda flow-meter with flow measured by a more accurate method. A calibrated Collins 9 liter bell spirometer was used for this purpose.

A constant flow of oxygen was passed through the flowhead of the Ohmeda flow-meter and into the spirometer. Flow was calculated as the rate of change of volume of gases in the spirometer with respect to time. The spirometer's chart recorder was used to keep track of the time and volume changes.

Because of drift in zero bias of the Ohmeda flow­

meter, values were obtained before each calibration measurement and subtracted from the readings. This allowed accuracy and drift to be accounted for separately. 25 calibration points were obtained and average values of calibration factors were calculated for positive and negative flows. An average calibration factor of 87.92

21 Liters/Volt with a standard error of 0.086 LPM was found for the positive flows while those of the negative flows were found to be 94.42 Liters/Volt and 0.107 LPM correspondingly. Figure 4.1 shows the flow reading of Ohmeda flow-meter in Volts, vs. actual flow in LPM. The 25 data points are also illustrated in this figure. To account for flow-meter's zero bias the value of this bias must be known and subtracted from the flow-meter's readings. The actual flow will therefore be calculated by:

Flow = 87.92 x Vou^. - Bias if Vout>0 (eq. 4.1a) Flow = 94.42 x VQu^. - Bias if Vout<0 (eq. 4.1b) where VQu^ = Output voltage of Ohmeda flow-meter

Flow = Actual flow through flow-meter's flowhead.

An Intel's system 310 micro-computer with the iSBX-311 analog input multimodule board installed, was used for data acquisition and processing. The iSBX-311 is a 16 channel, 12 bits analog to digital converter, specified to have an accuracy of ±0.035% of the full scale and ±1/2 of the least significant bit. Typical conversion speed is 50 sec.

Software Description

Source code for the program was written in PL/M 86 programming language. By using multi-tasking features of the iRMX 86 operating system it was possible to assign a high priority task to sampling the two channels and a

ACTUAL FLOW CLPM3

87.92

OHMEDA CVolts3

94.42

Figure 4.1. Flow-meter calibration data.

23 lower priority task to calculating and displaying the results. In this way continuous sampling is achieved and calculation and screen update are accomplished between samples. The program starts by sampling flow waveform until it detects the start of a breath. To avoid erroneous detection of noise as the start of a breath, a flow threshold of 5 LPM was used. In other words the flow­

meter's output signal must reach +5 LPM before the program detects the start of a breath. Once a breath is detected both flow and concentration are sampled until a downward crossing of the -5 LPM flow is detected. This signifies the end of inspiration and start of expiration. Again both signals are sampled until the start of next breath. In calculating uptake, the program takes into account the time delay between the gas analyzer's and the flow-meter's output by using equation 2.7.

The computer was programmed to sample each channel at a rate of 100 Hz. A sampling rate of 100 Hz was chosen in order to satisfy the Nyquist criterion which states that the sampling rate must be at least twice the highest frequency component of the sampled signal.

According to Webster [7] respiratory measurements have a frequency range from 0 to 40 Hz.

The program prompts the user for the time delay in the gas analyzer, and also for the flow-meter's

24 calibration information. Program outputs include breath to breath results of inspired and expired volume, inspired and end-tidal concentration of anesthetic, single breath uptake and cumulative uptake of anesthetic, elapsed time since the start of the program, and breathing rate. These are calculated as explained previously.

Flow-meter bias was calculated by using the values measured for inspired and expired volumes during the first breath. Assuming that inspired and expired volumes should be equal, the flow-meter's bias is the value which when subtracted from flow will equate the inspired and expired volumes.

CHAPTER 5 SYSTEM EVALUATION

The overall system described in the last section was evaluated by two procedures. The first procedure was designed to test the computer's ability to sample the two A/D channels correctly and perform the calculations properly. In this part the computer's timing was also tested. The second procedure was designed to test the overall system. This was accomplished by using an uptake simulation setup and comparing the expected uptake with the Uptake measured by the system.

Computer's Software/Hardware Tests

A Tektronix DC504 timer was used to measure the frequency of the computer clock. The test was repeated 8 times over the period of three days and the results showed a consistent frequency of 153.66KHz ± 17..

The analog to digital (A/D) sampling hardware and software were calibrated by applying a known D.C. voltage (measured by Tektronix 501 DMM) to the sampled channel and checking the digitized values. Readings were accurate plus or minus one least significant bit and showed a consistent bias of less than 2.0 mVolt which was taken into account

in flow and concentration conversions.

25

26 A feature of the software which required careful testing was the detection of the beginning of inspiration and expiration. To test this feature a D.C. voltage was applied to the flow channel during sampling and the voltage was slowly increased. The voltage was constantly monitored using a Tektronix 502 DVM. As the voltage passed 0.05V (corresponding to 5 LPM). the program indicated detection of inspiration. When the flow was reduced the sampling of the inspiration continued until the voltage reached -0.05V (corresponding to -5 LPM). At this time the program indicated the detection of expiration.

Overall System Evaluation

The system was tested in the laboratory for three simulated situations of emergence, induction, and zero uptake of anesthetic. The system's ability to accurately determine inspired and expired volumes, breathing rate, and breath to breath and cumulative anesthetic uptake was evaluated by comparing the measurement system results with the expected values from our simulation test setup. In the case of emergence and induction the test setup consisted of a Harvard respiration pump, an anesthetic machine with a Ohio 5000 vaporizer, and a calibrated 9-1 iter Collins spirometer with a mixing fan mounted inside the chamber (Figure 5.1). The spirometer was filled with approximately 8.0 Liters of oxygen and forane. The forane concentration

27 was measured by channel 1 of the gas analyzer and arbitrarily adjusted to a level between 1 to 57.. The flow­

meter and channel 2 of the gas analyzer were then connected between the spirometer and the ventilator to monitor flows and concentration of gas moving into and out of the spirometer. The ventilator pumped fresh gas (no anesthetic) into the spirometer which then pushed the same volume of mixed gas out. With each movement of gas into and out of the spirometer ("each breath"), the anesthetic concentration was reduced and eventually reached near zero.

During the induction of anesthesia the inspired concentration of anesthetic gases are higher than that of the expired gases. As the induction continues the inspiratory and expiratory concentrations approach an equilibrium. To simulate this situation in the setup of figure 5.1, the flow-meter was installed so that flow going into the spirometer (fresh gas) was considered an expiration and flow out of the spirometer (mixed with anesthetic) was considered an inspiration.

For emergence, the concentration of inspired gases is less than the anesthetic concentration of expired gases. To simulate this condition the flow-meter was reversed so that fresh gases into the spirometer

VENTILATOR FRESH GASES H' 7

EXHAUST

SPIROMETER

ADC MASS SPEC CH. 0

CH.2 CH. 1 INTEL

SYSTEM 310 MICROCOMPUTER

FLOW-METER CH. 1

Figure 5.1. Test system used for induction and emergence

s i mu1 at i on. w

00

29 represented an inspiration and anesthetic containing gases out of the spirometer represented an expiration.

To simulate zero uptake a slightly different test set up was used. Figure 5*2 shows the set up for this test. A Fraser Harlake model 701 ventilator was used to pump oxygen with anesthetic into and out of the spirometer. The flow-meter and port 2 of the gas analyzer were used to monitor flow and concentration as in the previous tests. Since the same gases were being cycled back and forth there was no change in the concentration which simulates zero uptake.

Expected values for concentration changes and uptake were calculated from the original anesthetic concentration in the spirometer and volume changes with each breath. Dead space mixing was minimized and (as will demonstrated later) included in the calculations for expected results. Anesthetic uptake by the water in the spirometer was measured in separate tests. It was found that the absorption of the anesthetic gas in water reaches an equilibrium after about 1 minute (figure 5.3).

Expected breath by breath uptake/loss of anesthetic by the spirometer was calculated as the increase/decrease in concentration of anesthetics times the volume of gases inside the spirometer:

U(i) = Vsp ( Csp(i) - Csp(i-1) ) (eq. 5.1)

SPIROMETER

FLOW-METER VENTILATOR

MASS SPEC

CH.2 CH. 1 INTEL

SYSTEM 310 MICROCOMPUTER

ADC CH. 0

CH. 1

F i gure 5.2. Test system used for zero-uptake simulation. U) o

31 Forane a

conc.

C/.3 -k.

5 --

4 "

3 -

I --

+->

Time Cmin.3

Figure 5.3. Uptake of anesthetic by the spirometer water.

32 where U(i) = uptake per breath

Csp(i) = current anesthetic concentration Csp(i-l)= concentration before current breath Vsp = volume of the spirometer

Vgp was measured prior to the test and was found to be 7785=78 c.c. Csp(i) can be calculated by:

r

...

-

ds'*

in

V

ds»

spl

-

> ,

C ( i > = Z (eq. 5.2)

V

sp

where dV = volume of gases entering and leaving spirometer Cin = concentration of gases entering spirometer

Vds = dead sPace volume

The inspired and expired volumes (dV) for each test was measured by reading the volume on the spirometer's chart.

This volume had been calibrated using a 3.0 liter calibrating syringe prior to the tests. Concentration of gases into the spirometer (Cⁱⁿ) is equal to zero for the induction and emergence tests. represents the volume of tubings where no mixing of the inspired gases occur.

This is the volume between the gas analyzer sampling channel 2, and the mixing chamber of the spirometer. This

volume was measured and found to be 125±2 c.c.

Notice that by using equations 5.1 and 5.2 and by knowing the initial concentration of anesthetics inside the spirometer and the concentration of gases entering the

33

spirometer, the expected breath by breath uptake can be calculated:

Csp(0> = initial concentration (eq. 5.3)

dV x Cln • vsp x csp<°>

CSD(1) = (eq. 5.4)

P vsp + =<V

U(1) = vsp < Csp^¹) - ^csp<°> > <^ecl- ⁵-⁵>

d V x C + vs p x Cs p( 1 )

C (2) = p p (eq. 5.6)

^sp ⁺

U(2) = V^sp <C^Sp(2) - C^sp(l) ) (eq. 5.7)

During emergence tests, the spirometer simulates the patient and the anesthetic uptake is equal to the uptake by the spirometer (eq. 5.1). During induction tests, the spirometer simulates the anesthetic delivery system and uptake of anesthet i c by pat i ent i s negat i ve that of the spirometer. For the case of zero uptake, use of equations 5.1 and 5.2 is not necessary because constant concentration and zero uptake is expected.

10 runs of 40 "breaths" were performed for each of induction, emergence, and zero uptake. The tests were performed over a period of 3 weeks. Comparisons were made

34 between expected and computer generated results. For the cases of induction and emergence* correlation between predicted uptake and uptake measured by the system was calculated using linear regression analysis. In the case of zero uptake, standard deviation about the predicted zero uptake was calculated.

CHAPTER 6

RESULTS

Tables 6.1a and 6.1b show a typical breath by breath results of inspired and expired volumes, concentrations, breathing rate, and uptake measurements during emergence tests. Included in these tables are the corresponding errors between the measurement and its expected value. The expected value for the volumes is that read from the spirometer's chart during the particular test. The expected value of the breathing rate is calculated during each test by reading the time for a few breaths on the time scale of the spirometer (previously calibrated) and dividing the number of breaths by time. In the case of concentrations and uptake the expected values are calculated using equations 5.1 and 5.3 explained in the previous section.

Overal1 test results for the case of emergence are included in tables 6.2a and 6.2b. Table 6.2a includes mean measured inspired and expired volumes and their standard deviation plus the error between the mean and expected values. Table 6.2b includes the mean measured breathing rate and the cumulative uptake and the percent difference

35

36 TABLE 6,. I A- Breath to breath results for emergence trial

#8.

BREATH V i ns 7.V i ns Vexp 7.Vexp B.R. %B.R.

#

1 0.77 0.13 -.75 2.72 7.0 3.12

2 0.76 1.43 -.73 5.32 7.0 3.71

3 0.77 0.13 -.72 6.61 7.0 3.26

4 0.77 0.13 -.73 5.32 7.0 3.41

5 0.78 1.17 -.73 5.32 7.0 3.12

6 0.79 2.46 -.73 5.32 7.2 6.82

7 0.79 2.46 -.71 7.91 6.7 0.74

8 0.79 2.46 -.72 6.61 6.9 2.97

9 0.79 2.46 -.73 5.32 6.9 2.37

10 0.79 2.46 -.75 2.72 6.9 2.52

1 1 0.80 3.76 -.75 2.72 6.9 2.23 12 0.80 3.76 -.78 1 . 17 6.9 1 .93 13 0.80 3.76 -.76 1 .43 6.9 1 .93 14 0.79 2.46 -.73 5.32 6.9 1 .93 15 0.79 2.46 -.76 1.43 6.9 1 .93 16 0.80 3.76 -.77 0. 13 6.8 0.89 17 0.81 5.06 -.74 4.02 6.8 1 .48 18 0.81 5.06 -.76 1 .43 6.8 0.89 19 0.81 5.06 -.74 4.02 6.8 1 .48

20 0.80 3.76 -.72 6.61 6.8 0.89

21 0.81 5.06 -.71 7.91 6.9 1 .93

22 0.82 6.36 -.72 6.61 6.7 0.00

23 0.81 5.06 -.72 6.61 6.8 0.45

24 0.81 5.06 -.75 2.72 6.8 1 .48

25 0.82 6.36 -.75 2.72 6.7 0.45

26 0.82 6.36 -.74 4.02 6.7 0.00

27 0.81 5.06 -.74 4.02 6.8 0.45

28 0.81 5.06 -.76 1 .43 6.8 0.45 29 0.81 5.06 -.77 0. 13 6.8 0.45 30 0.81 5.06 -.76 1 .43 6.7 0.00 31 0.81 5.06 -.76 1 .43 6.7 0.00 32 0.81 5.06 -.77 0. 13 6.7 0.89

33 0.81 5.06 -.76 1.43 6.7 0.45

34 0.81 5.06 -.77 0. 13 6.7 0.45 35 0.81 5.06 -.79 2.46 6.8 1 .48 36 0.83 7.65 -.76 1 .43 6.6 1 .78

EXPECTED .77 0.77 6.7

37 TABLE 6.1 B- Breath to breath results for emergence trial

#8.

BREATH Cins Cet Csp Uptake Uptake 7.Uptake

# measured measured calc. measured calc. error [7.] [7.] [7.] [c.c. Vapor]

1 4.32 0.04 4.03 -25.80 -24.52 5.21 2 4.04 0.04 3.73 -23.00 -22.74 1 .13 3 3.70 0.04 3.46 -20.80 -21.09 1 .39 4 3.42 0.04 3.21 -19.90 -19.56 1.73 5 3.20 0.03 2.98 -18.10 -18.14 0.23 6 3.06 0.03 2.76 -16.60 -16.82 1 .34 7 2.78 0.03 2.56 -14.70 -15.60 5.79 8 2.54 0.03 2.38 -14.00 -14.47 3.26 9 2.42 0.03 2.20 -13.00 -13.42 3.14 10 2.25 0.03 2.04 -12.50 -12.45 0.43 11 2.06 0.02 1.89 -11.50 -11.54 0.38 12 1.92 0.03 1.76 -11.20 -10.71 4.62 13 1 .79 0.02 1.63 -10.00 -9.93 0.72 14 1 .67 0.03 1.51 -9.00 -9.21 2.26 15 1 .55 0.02 1.40 -8.60 -8.54 0.71 16 1 .44 0.02 1.30 -7.90 -7.92 0.25 17 1.31 0.02 1.21 -7.10 -7.34 3.33 18 1 .22 0.01 1.12 -6.60 -6.81 3.11 19 1 .15 0.02 1.04 -6.10 -6.32 3.44 20 1 .06 0.01 0.96 -5.40 -5.86 7.83 21 1 .00 0.02 0.89 -5.00 -5.43 7.98 22 0.93 0.02 0.83 -4.60 -5.04 8.72 23 0.86 0.01 0.77 -4.30 -4.67 7.99 24 0.81 0.01 0.71 -4.20 -4.33 3. 10 25 0.75 0.01 0.66 -3.80 -4.02 5.47 26 0.69 0.01 0.61 -3.60 -3.73 3.43 27 0.64 0.02 0.57 -3.40 -3.46 1 .66 28 0.60 0.01 0.53 -3.20 -3.21 0.20 29 0.55 0.01 0.49 -3.00 -2.97 0.88 30 0.52 0.01 0.45 -2.70 -2.76 2. 10 31 0.48 0.01 0.42 -2.60 -2.56 1 .65 32 0.44 0.01 0.39 -2.40 -2.37 1 . 18 33 0.41 0.01 0.36 -2.20 -2.20 0.00 34 0.39 0.01 0.33 -2.10 -2.04 2.93 35 0.36 0.00 0.31 -2.00 -1.89 5.70 36 0.34 0.01 0.29 -1 .80 -1 .75 2.57

Table 6.2.A- Results of laboratory tests of the measurement system during simulated anesthetic emergence.

RIAL EXPECTED MEAN S. D. %Vins MEAN S. D. %Vexp

# ^{VOLUME Vins Vins ERROR Vexp Vexp ERROR}

[L] [L] [L] [L] [L]

1 0.77 0.82 0.0917 6.13 -.77 0.0980 0.39 2 0.77 0.75 0.1261 2.22 -.77 0.1433 0.30 3 0.77 0.75 0.1214 2.90 -.77 0.0639 0.37 4 0.75 0.76 0.0047 0.71 -.72 0.0218 3.76 5 0.75 0.75 0.0408 0. 11 -.72 0.0586 4.19 6 0.75 0.73 0.0686 2.48 -.73 0.0050 2.00 7 0.77 0.82 0.0003 6.53 -.75 0.0267 3.03 8 0.77 0.80 0.0106 3.83 -.75 0.0256 3.30 9 0.75 0.71 0.0086 5.15 -.74 0.0811 1.19 10 0.75 0.74 0.0147 1.96 -.75 0.0558 0.56

ui 00

Table 6.2.B- Results of laboratory tests of the measurement system during simulated anesthetic emergence.

TRIAL EXPECTED MEAN S.D. 7.B.R. CALC- MEAS- CORR- %UPTAKE

# B.R. B.R. B.R. ERROR ULATED URED ECTED ERROR UPTAKE UPTAKE UPTAKE

[BPM] [BPM] [BPM] [ c.c. Vapor ]

1 5.2 5.02 0.2231 2.81 -327.42 -315.70 -324.08 1.02 2 5.7 5.83 0.2617 1.72 -39.25 -39.90 -39.00 0.64 3 6.2 5.99 0.2511 2.58 -100.30 -105.20 -102.56 2.25 4 6.2 6.22 0.4350 1 .06 -234.90 -224.10 -230.19 2.01 5 5.3 5.50 0.5853 3.28 -272.21 -273.60 -279.02 2.50 6 6.5 6.59 0.1750 1.31 -129.97 -122.70 -122.73 5.57 7 6.7 6.74 0.1511 0.02 -342.96 -326.60 -345.71 0.80 8 6.7 6.83 0.2386 1.36 -315.45 -312.70 -327.33 3.77 9 6.3 6.28 0.0739 0.03 -234.67 -233.30 -227.97 2.86 10 7.0 6.88 0.0292 1.09 -277.99 -270.60 -268.90 3.27

40 between the measured and expected values. These tables include the results of all of the performed emergence tests.

Typical breath to breath results of induction tests are shown in tables 6.3a and 6.3b and the overall results are shown in tables 6.4a and 6.4b. All the parameters and their corresponding calculations are the same as with emergence. Breath by breath uptake decreases during each breath for induction. An example of the change over one induction test is shown in figure 6.1.

Tables 6.5a and 6.5b demonstrate a typical breath to breath result of zero uptake test. Tables 6.6a and 6.6b demonstrate the overal1 results of the zero uptake tests.

Inspection of the data revealed that zero bias drifts in the flow-meter produced a mismatch in inspired and expired volumes. To correct the errors caused by this bias variation, a bias correction parameter was calculated for each breath and subtracted from the measured uptake for that breath. The corrected results for the cases of induction, emergence and, zero uptake are included in tables 6.2, 6.4, and 6.6 respectively.

Cumulative uptake (predicted vs. corrected) agreed closely. Regression analysis performed on al1 20 induction and emergence uptake data (10 induction and 10 emergence) produced a least squares fit line with a slope of 1.003

41 TABLE 6.3 A- Breath to breath results for induction trial

#2.

BREATH Vins 7.V i ns Vexp 7. Vexp B.R. 7.B. R.

# [L] ERROR [L] ERROR [BPM] ERROR

1 0.74 1.33 -.76 1.33 7.0 3.26

2 0.74 1.33 -.75 0.00 7.0 3.71

3 0.76 1.33 -.75 0.00 7.0 3.26

4 0.79 5.33 -.75 0.00 7.0 3.41

5 0.76 1.33 -.75 0.00 7.0 3. 12

6 0.75 0.00 -.75 0.00 7.0 3.26

7 0.75 0.00 -.74 1.33 6.9 2.82

8 0.73 2.67 -.75 0.00 6.9 2.82

9 0.73 2.67 -.75 0.00 6.9 2.67

10 0.73 2.67 -.74 1 .33 6.9 2.37 1 1 0.76 1 .33 -.74 1.33 6.9 2.52 12 0.77 2.67 -.74 1 .33 6.9 2.23

13 0.78 4.00 -.75 0.00 6.9 2.52

14 0.78 4.00 -.74 1 .33 6.9 1 .93

15 0.77 2.67 -.74 1.33 6.9 2.37

16 0.78 4.00 -.73 2.67 6.8 1 .48 17 0.78 4.00 -.74 1.33 6.8 1 .48 18 0.78 4.00 -.74 I .33 6.9 1 .93 19 0.77 2.67 -.73 2.67 6.8 1 .34 20 0.78 4.00 -.73 2.67 6.8 1 .04 21 0.78 4.00 -.74 1.33 6.8 1 .48

22 0.77 2.67 -.73 2.67 6.8 0.89

23 0.78 4.00 -.74 1 .33 6.8 1 .34

24 0.81 8.00 -.75 0.00 6.8 0.89

25 0.82 9.33 -.75 0.00 6.8 0.45

26 0.81 8.00 -.75 0.00 6.8 0.89

27 0.82 9.33 -.76 1.33 6.8 0.45

28 0.80 6.67 -.76 1 .33 6.8 0.45

29 0.81 8.00 -.75 0.00 6.8 0.45

30 0.80 6.67 -.76 1 .33 6.8 0.45

31 0.81 8.00 -.75 0.00 6.8 0.45

32 0.81 8.00 -.75 0.00 6.8 0.45

33 0.79 5.33 -.75 0.00 6.7 0.00

34 0.81 8.00 -.75 0.00 6.7 0.00

35 0.83 10.67 -.76 1.33 6.7 0.00 36 0.81 8.00 -.76 1 .33 6.7 0.00

EXPECTED .75 0.75 6.7

42 TABLE 6.3 B- Breath to breath results for Induction trial

#2.

BREATH Clns Cet Csp Uptake Uptake %Upta

#

[%] [%] [%]

1 0.03 3.36 3. 12 17.40 18.34 5. 13 2 0.03 3.12 2.90 16.70 17.05 2.06 3 0.02 2.85 2.69 15.80 15.85 0.33 4 0.03 2.70 2.50 15.50 14.74 5. 17 5 0.02 2.48 2.33 13.80 13.70 0.72 6 0.02 2.31 2. 16 12.50 12.74 1.87 7 0.02 2.15 2.01 11 .70 1 1.84 1.21 8 0.02 2.02 1.87 10.40 11.01 5.55 9 -.02 1 .93 1.74 9.70 10.24 5.24 10 0.01 1 .76 1 .62 9.10 9.52 4.38 1 1 0.01 1 .61 1 .50 9.00 8.85 1 .72 12 0.02 1 .52 1 .40 8.50 8.23 3.33 13 0.01 1.38 1 .30 7.80 7.65 1 .99 14 0.01 1 .32 1.21 7.40 7. 1 1 4.08 15 0.01 1 .22 1 . 12 6.80 6.61 2.87 16 0.02 1.10 1 .04 6.40 6.15 4. 14 17 0.02 1 .07 0.97 6.00 5.71 5.01 18 0.01 0.96 0.90 5.60 5.31 5.43 19 0.01 0.79 0.84 5.20 4.94 5.30 20 0.01 0.80 0.78 4.80 4.59 4.55 21 0.01 0.68 0.73 4.40 4.27 3.08 22 0.01 0.68 0.67 4.00 3.97 0.80 23 0.01 0.59 0.63 3.80 3.69 3.00 24 0.00 0.61 0.58 3.70 3.43 7.87 25 0.01 0.58 0.54 3.50 3. 19 9.75 26 0.01 0.55 0.50 3.20 2.96 7.93 27 0.00 0.52 0.47 3.00 2.76 8.84 28 0.01 0.47 0.44 2.80 2.56 9.26 29 0.00 0.43 0.40 2.60 2.38 9. 13 30 0.00 0.41 0.38 2.40 2.21 8.35 31 0.01 0.36 0.35 2.20 2.06 6.84 32 0.00 0.36 0.33 2.10 1.91 9.69 33 0.00 0.32 0.30 1 .90 1.78 6.75 34 0.00 0.30 0.28 1.80 1.65 8.78 35 0.01 0.29 0.26 1.70 1.54 10.50 36 0.00 0.26 0.24 1 .60 1.43 1 1 .87

Table 6.4.A- Results of laboratory tests of the measurement system during simulated anesthetic induction.

TRIAL EXPECTED MEAN S. D. %Vins MEAN S. D. %Vexp

#

[L] [L] [L] [L] [L]

1 0.75 0.80 0.0075 7.00 -.76 0.0192 1.44 2 0.75 0.78 0.0003 4.04 -.75 0.0033 0.44 3 0.77 0.81 0.0050 4.44 -.78 0.0186 1.37 4 0.77 0.78 0.0467 1.63 -.78 0.0219 1.45 5 0.77 0.82 0.0574 6. 16 -.73 0.0474 4.86 6 0.77 0.74 0.0044 4.51 -.76 0.0353 0.72 7 0.77 0.73 0.0208 5.16 -.78 0.0003 1.41 8 0.78 0.83 0.0608 6.67 -.76 0.0261 1.93 9 0.78 0.80 0.0081 2.46 -.76 0.0303 2.46 10 0.78 0.81 0.0387 3.83 -.74 0.0590 4.86

Table 6.4.B- Results of laboratory tests of the measurement system during simulated anesthetic induction.

TRIAL EXPECTED MEAN S.D. 7.B.R. CALC­ MEAS­ CORR­ 7.UPTAKE

# ^{B.R. B.R. B.R. ERROR ULATED URED ECTED ERROR} UPTAKE UPTAKE UPTAKE

[BPM] [BPM] [BPM] [ c.c Vapor

]

1 6.8 6.86 0.1161 0.94 271.10 277.40 274.55 1.27 2 6.7 6.85 0.1611 1.62 241.98 244.80 240.79 0.49 3 6.7 6.76 0.1586 0.32 210.86 210.40 207.82 1.44 4 6.7 6.69 0.0889 0.73 150.45 155.60 155.70 3.49 5 6.4 6.12 0.3082 4.35 282.31 288.80 279.33 1.05 6 6.4 6.37 0.0697 0.46 321.89 309.60 317.69 1.31 7 6.2 6.17 0.1475 0.37 307.54 291.90 302.24 1.73 8 6.5 6.36 0.1053 2.54 261.34 265.10 259.20 0.82 9 6.3 6.27 0.1314 0.09 213.09 212.70 211.07 0.95 10 6.4 6.46 0.1244 0.87 349.43 338.60 332.98 4.71

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46 TABLE 6.5 B- Breath to breath results for zero-uptake

trial #4.

BREATH Cins Cet Csp Uptake Uptake Uptake

# measured measured 1 ca1c. measured calc. error

[%] [%]

1 1.91 1.92 1.92 0.50 0.00 0.50 2 1.93 1.92 1.92 0.40 0.00 0.40 3 1.93 1.94 1.92 0.40 0.00 0.40 4 1.91 1.93 1.92 0.40 0.00 0.40 5 1.92 1.92 1.92 0.50 0.00 0.50 6 1.91 1.92 1.92 0.20 0.00 0.20 7 1.92 1.93 1.92 0.20 0.00 0.20 8 1.92 1.92 1 .92 0.20 0.00 0.20 9 1.92 1.92 1.92 -0.10 0.00 0. 10 10 1.92 1.94 1 .92 0.10 0.00 0.10 1 1 1.92 1.91 1.92 0.20 0.00 0.20 12 1.92 1.92 1.92 0.10 0.00 0. 10 13 1.91 1.91 1.92 -0.10 0.00 0.10 14 1 .89 1 .90 1.92 -0.20 0.00 0.20 15 1 .89 1 .89 1.92 -0.10 0.00 0. 10 16 1 .89 1.90 1 .92 -0.20 0.00 0.20 17 1 .89 1 .89 1.92 -0.20 0.00 0.20 18 1 .90 1.91 1 .92 -0.40 0.00 0.40 19 1 .88 1.89 1 .92 -0.20 0.00 0.20 20 1 .90 1.89 1 .92 -0.30 0.00 0.30 21 1 .90 1 .89 1.92 -0.30 0.00 0.30 22 1.88 1.88 1 .92 -0.30 0.00 0.30 23 1 .90 ,1 .89 1 .92 -0.40 0.00 0.40 24 1.88 1.89 1 .92 -0.50 0.00 0.50 25 1 .88 1 .89 1.92 -0.60 0.00 0.60 26 1.88 1 .88 1 .92 -0.50 0.00 0.50 27 1 .87 1.87 1 .92 -0.50 0.00 0.50 28 1 .89 1.88 1 .92 -0.40 0.00 0.40 29 1 .88 1 .88 1.92 -0.70 0.00 0.70 30 1.88 1 .88 1 .92 -0.50 0.00 0.50 31 1.88 1.88 1 .92 -0.50 0.00 0.50 32 1.88 1.89 1 .92 -0.50 0.00 0.50 33 1.89 1.88 1 .92 -0.40 0.00 0.40 34 1.88 1.88 1 .92 -0.40 0.00 0.40 35 1 .88 1.88 1 .92 -0.30 0.00 0.30 36 1.88 1.88 1 .92 -0.40 0.00 0.40